Prevalence of COVID-19 outcomes in patients referred to opioid agonist treatment centers.

Background: Coronavirus disease (COVID-19) is a mild to severe infectious respiratory illness caused by the SARS-CoV-2 virus. Based on the numerous pieces of evidence regarding the role of opioids in immune function, viral replication, and virus-mediated pathology, we decided to assess the incidence and severity of COVID-19 outcomes in people undergoing opioid maintenance treatment. Methods: This is a prospective, descriptive, multi-center study that included 452 patients undergoing maintenance treatment in opioid agonist treatment (OAT) clinics in different cities of Iran. Demographic information, underlying disease, history of maintenance treatment, type of drug used, history of addiction, smoking, and the kind of substance abused, were recorded. A physician evaluated the COVID-19 symptoms, and the severity of the disease was defined based on the number of observed symptoms. Results: The results have not shown any significant difference in the severity of COVID-19 symptoms in different nationalities, gender, and treatment groups. Furthermore, the history of drug abuse, including time and type of abuse and smoking, has not indicated any significant association with the occurrence of symptoms. Only the severity of COVID-19 in the mentioned cities (first and second follow-up: p < 0.001) and individuals with a history of underlying disease (first follow-up: p = 0.020; second follow-up: p = 0.043) were significantly different. Conclusion: Our results have demonstrated that the severity of symptoms in people with the underlying disease was significantly higher than in others. But there is no association between sex, race, treatment groups, and abuse history with the severity of COVID-19 symptoms in methadone maintenance treatment (MMT) patients.

Prevalence of enteric adenovirus and co-infection with rotavirus in children under 15 years of age with gastroenteritis in Qom, Iran.

Aim: The current study is the first performed in Qom to determine the prevalence of adenovirus and co-infections with rotavirus in children aged <15 years with gastroenteritis symptoms. Background: Gastroenteritis-associated viral infections are a cause of death among young children worldwide, especially in developing countries. The Adenovirus species F (40 and 41) are responsible for a range of acute diarrhea cases among infants and children. Methods: Over a period of 9 months, a total of 130 children suffering from intestinal problems who referred to the infectious ward of Children's Hospital were enrolled in the current study. After clinical examination and collection of demographic information, fecal samples were obtained from the patients. Viral genomes were extracted with a commercial kit and amplified and typed by adenovirus-specific PCR assay. Adenovirus-positive samples were also evaluated for co-infection with rotavirus. Results: Patients had a mean±SD age of 2.66±2.72 years; 63.1% of patients were male and 36.9% were female. Adenovirus infection was identified in 23 cases (17.7%), 21 (91.0%) and 2 (9.0%) of which were type 41 and type 40, respectively. Fever was the most common clinical manifestation among adenovirus-positive patients. No significant difference was observed between adenovirus infection and clinical symptoms, seasonal pattern, or serum laboratory results. Co-infection was found in only 5 cases (21.7%). Conclusion: This study was the first to demonstrate adenovirus infection with a relatively high prevalence among children, especially infants, in Qom. The findings further revealed co-infection with rotavirus, indicating a health problem in this region.

Magnesium supplementation and insulin resistance in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a multifactorial disease affecting the immune system and many tissues in the body. This study aimed to evaluate the effect of magnesium supplementation on insulin resistance and fasting blood sugar (FBS) of patients with RA. In this prospective uncontrolled before-after study, RA patients referring to Rheumatology clinics of Qom City from January 2020 to January 2021 were evaluated. First, the patients received the routine rheumatoid arthritis treatment including 5 mg Prednisolone and 200mg Hydroxychloroquine daily for 6 months and FBS and insulin levels were measured after. Then, they received the routine arthritis rheumatoid treatment in addition to 300 mg/day oral Magnesium sulfate for 6 months and then, FBS and insulin levels were measured. The Homeostasis Model Assessment of insulin resistance (HOMA-IR) was used for determining insulin resistance. Thirty five patients with RA and the mean age of 49.83±2.58 years were enrolled. Twenty eight cases (80%) were female and 7 cases (20%) were male. The mean HOMA-IR before and after consumption of oral magnesium were 3.04±0.29 and 2.43±0.19, respectively. Statistically significant differences were found between FBS, insulin and HOMA-IR before and after consumption of oral magnesium (p<0.05). Our data suggested that magnesium supplementation reduces FBS, insulin and HOMA-IR in patients with rheumatoid arthritis. Thus, magnesium supplements may be an alternative method for prevention of type 2 diabetes in RA patients.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

BACKGROUND: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. METHODS: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. RESULTS: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. CONCLUSION: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

Detection and characterization of rotavirus G and P types from children with acute gastroenteritis in Qom, central Iran.

AIM: The aim of the study is to estimate the burden of Rotavirus gastroenteritis as well as predominant genotypes of Rotavirus among children less than 5 years of age referring to Pediatric University Hospital in Qom, Iran. BACKGROUND: Gastroenteritis is the fourth most common cause of death and accounts for 16% of all deaths in children <5 years of age worldwide. METHODS: During two years, 130 patients referring to a pediatric hospital were enrolled in this study. After RNA extraction, Rotaviruses were detected by the VP6 gene. Then, G-typing (G1, G2, G3, G4, G8, G9, and G12) and P-typing (P4, P6, and P8) were performed using RT-PCR and specific primers. RESULTS: The results of the PCR revealed that from a total of 130 patients, 22 cases (16.9%) showed positive VP6 by RT-PCR. G1 was mostly the predominant serotype (27%), accounting for 22% of all VP7-positive isolates, followed by G9 (18%), G2 (9%), G3 (9%), and G4 (9%). None of the strains revealed the presence of G8 genotype (0%), and 5 specimens (23%) were non-typable. The frequency of P typing was P8 (50%), P6 (23%), P4 (14%), and 3 samples were P-non-typable (13%), respectively. The dominant G-P combination was G1 [8] (32%). CONCLUSION: Such studies based on typing methods assists in the Rotavirus vaccine introduction by policymakers and design of new effective vaccines.

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase [BTK] and 6 µ heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with µ heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with µ heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis.

BACKGROUND: The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. METHOD: The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. RESULTS: Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. CONCLUSIONS: During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency.

BACKGROUND: Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. OBJECTIVES: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. METHODS: Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. RESULTS: The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs. CONCLUSIONS: This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.

Cernunnos deficiency associated with BCG adenitis and autoimmunity: First case from the national Iranian registry and review of the literature.

Non-homologous end-joining (NHEJ) is a pathway that repairs double-strand breaks (DSB) in DNA and plays a vital role in V(D)J recombination of immunoglobulin genes. Cernunnos is a DNA repair factor that is involved in nonhomologous end-joining (NHEJ) process. Impairment in Cernunnos leads to a genetic disease characterized by neural disorders, immunodeficiency and increased radiosensitivity. We herein describe a severe combined immunodeficiency (SCID) patient with T- B+ phenotype who had a mutation in Cernunnos gene and manifested recurrent infections, microcephaly and growth retardation with hypogammaglobulinemia. Furthermore, our patient was associated with BCG adenitis and autoimmunity that less is observed in patients with Cernunnos deficiency. In contrast to previous reported Cernunnos-deficient patients, our patient had normal B-cell number along with normal IgA and IgM, suggesting a leaky form of the Cernunnos deficiency due to residual count of B cells in our patient. Cernunnos deficiency should be considered in children with recurrent bacterial infections, microcephaly and growth retardation, in spite of having normal B-cell as well as normal IgM and IgA level.

Comparison of Bone Mineral Density in Common Variable Immunodeficiency and X-Linked Agammaglobulinaemia Patients.

BACKGROUND: Primary antibody deficiency (PAD) is the most common group of primary immunodeficiency disorders, resulting from different defects in the development and function of B cell lineage. Common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA) are two of the major types of PADs. Optimal growth and subsequently bone health could potentially compromise due to the interference of several factors in PAD with childhood onset. In the present study, our aim was to evaluate bone mineral density (BMD) of patients with CVID and XLA. METHODS: BMD of 37 CVID and 19 XLA patients was examined. Total BMD was determined by dual-energy X-ray absorptiometry and the calculated scores were compared internally and externally with age-sex matched and ethnic-specific reference. Related factors associated with bone density including immune-related complications, serum calcium, phosphate, total alkaline phosphatase, 25(OH) vitamin D and parathyroid hormone levels were recorded. RESULTS: The median age at the time of study was 20 years among all patients and was not statistically different between CVID and XLA groups and the mean of body mass index (BMI) was 19.4±4.6 kg/cm². Thirty-eight (67.9%) of total patients had normal BMD and 18 (32.1%) patients had a low BMD. BMI was positively correlated with BMD at lumbar spine and femoral neck. The number of low BMD patients in CVID (40.5%) group was more than the XLA (15.8%). CONCLUSION: Beside nutritional, gastrointestinal and infectious complications which are shared in both groups of patients, CVID patients are more prone to alteration of BMD due to association with lymphoproliferative and endocrine diseases. Therefore routine evaluation of bone density and treatment adjustment should be considered in all PAD patients particularly in CVID patients.

Ethnomedicine for neonatal jaundice: A cross-sectional survey in Qom, Iran.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Medicine (TM) is popularly used for neonatal jaundice in Iran. OBJECTIVE: to provides evidence for characteristics of traditional medicine use in the treatment of neonatal jaundice in Qom, Iran. MATERIALS AND METHODS: Field surveys were carried out during July 2015 - August 2015 in Qom through structured questionnaire in Persian from 212 parents of children with neonatal jaundice. All plant species recorded for the treatment of neonatal jaundice were sampled. Samples were identified by a botanist and obtained a voucher specimens number and deposited in the Shiraz School of Pharmacy Herbarium. The information such as scientific name, family, local name, parts used and preparation method were provided. The Use Value (UV), Frequency of Citation (FC), Relative Frequency of Citation (RFC) and Relative Family Importance Value (FIV) are also calculated. RESULTS: In total, 165 (78%) of participants reported the use of traditional methods for their neonates. The use of herbal remedies was the most popular form of these traditional interventions. A total of 8 plant species belonging to 7 families were identified. Cotoneaster nummularioides Pojark. Cichorium intybus L. Alhagi maurorum Medik. Descurainia sophia (L.) Webb ex Prantl were most frequent herbs used by neonates and their feeding mother to treat jaundice. Manna was the most popular plant part and distillation and soaking were most frequent preparation methods in these patients. The use of TM in these patients is associated with their previous experience on TM use and their view on its potential risk. CONCLUSIONS: This study provided information on the prevalence, associated factors and characteristics of traditional medicine use along with ethnomedicinal knowledge from Qom in Iran on neonatal jaundice.